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Blood brain barrier (BBB) disruption is an integral feature of numerous neurological diseases with infectious, inflammatory, neoplastic and vascular components. It is of particular interest in the immune mediated neurological diseases multiple sclerosis (MS), acute disseminated encephalomyelitis (ADEM), and acute hemorrhagic leukoencephalitis (AHLE). In particular, AHLE is associated with very high mortality. A fundamental question in these diseases is the extent inflammatory immune cells contribute to CNS vascular permeability. This lack of understanding currently undermines therapeutic approaches to ameliorate uncontrolled BBB disruption. In this review, we highlight the current experimental model systems available to address the contribution of inflammatory cells in BBB disruption. The contribution of T cells and other immune cell subsets in altering blood brain barrier tight junctions in the experimental autoimmune encephalomyelitis (EAE), lipopolysaccharide (LPS), and virus induced CNS vascular permeability model systems is also addressed. Results obtained from the use of these model systems have put forward a defined role for neutrophils, CD4 and CD8 T cells and vascular endothelial growth factor (VEGF) in BBB disruption. Based on these findings, we describe models in which immune cells engage and alter CNS cell types of the neurovascular unit and define future avenues of research. Acute disseminating encephalomyelitis (ADEM) and acute hemorrhagic leukoencephalitis (AHLE) are demyelinating diseases that usually present shortly after infections or vaccination (Callen et al., 2009; Gibbs et al., 2005). ADEM typically has an overall favorable prognosis, with 60-80% of patients showing a complete recovery (Dale et al., 2000; Gibbs et al., 2005; Rust, 2000; Tenembaum et al., 2002). AHLE, which is also known as Hurst’s disease, has been considered a severe form of ADEM and has a very poor prognosis, usually resulting in death in 2-14 days (Geerts et al., 1991; Hart & Earle 1975; Pinto et al., 2011; Posey et al., 1994; Suchowersky et al., 1983). This disease is characterized by extensive BBB disruption and microhemorrhage formation. Typical acute symptoms of AHLE include fever, malaise, and headache, followed by a rapid progression of multifocal neurologic signs

intech ebooks

Experimental Model Systems to Define Mechanisms of Immune-Mediated Blood Brain Barrier Disruption in Acute Disseminated Encephalomyelitis (ADEM) and Acute Hemorrhagic Leukoencephalitis (AHLE)